SPECT Imaging with Tc-99m-Labeled HYNIC-FAPI-04 to Extend the Differential Time Window in Evaluating Tumor Fibrosis
The so-far used Ga-68- or F-18-labelled tracers are of a relative short time window in differentiating tumor fibrosis. SPECT applicable imaging probe, <sup>99m</sup>Tc-HYNIC-FAPI-04, was synthesized and evaluated in tumor cells and animal models of FAP-positive glioma and FAP-negative he...
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MDPI AG
2023-03-01
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| Series: | Pharmaceuticals |
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| Online Access: | https://www.mdpi.com/1424-8247/16/3/423 |
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| author | Xiu Luo Zhe Zhang Chao Cheng Tao Wang Danzhou Fang Changjing Zuo Gengbiao Yuan Rou Li Xiao Li |
| author_facet | Xiu Luo Zhe Zhang Chao Cheng Tao Wang Danzhou Fang Changjing Zuo Gengbiao Yuan Rou Li Xiao Li |
| author_sort | Xiu Luo |
| collection | DOAJ |
| description | The so-far used Ga-68- or F-18-labelled tracers are of a relative short time window in differentiating tumor fibrosis. SPECT applicable imaging probe, <sup>99m</sup>Tc-HYNIC-FAPI-04, was synthesized and evaluated in tumor cells and animal models of FAP-positive glioma and FAP-negative hepatoma, and then compared with <sup>18</sup>F-FDG or <sup>68</sup>Ga-FAPI-04 PET/CT. The radio-labeling rate of <sup>99m</sup>Tc-HYNIC-FAPI-04 was greater than 90%, and the radiochemical purity was >99% after purification with sep-pak C18 column. In vitro cell uptake experiments of <sup>99m</sup>Tc-HYNIC-FAPI-04 showed good FAP binding specificity, and the cellular uptake significantly decreased when blocked by DOTA-FAPI-04, reflecting the similar targeting mechanism of HYNIC-FAPI-04 and DOTA-FAPI-04. SPECT/CT imaging showed that U87MG tumor was distinguishable and of a high uptake of <sup>99m</sup>Tc-HYNIC-FAPI-04 (2.67 ± 0.35 %ID/mL at 1.5 h post injection (h P.I.), while tumor signal of FAP-negative HUH-7 was as low as 0.34 ± 0.06 %ID/mL. At 5 h P.I., U87MG tumor was still distinguishable (1.81 ± 0.20 %ID/mL). In comparison, although U87MG tumor was of obvious <sup>68</sup>Ga-FAPI-04 uptake and clearly visible at 1 h P.I., the tumorous radioactive signals were fuzzy at 1.5 h P.I. <sup>99m</sup>Tc-HYNIC-FAPI-04 specifically bound to FAP-positive tumors and qualified with the ability of evaluating tumor fibrosis over longer time windows. |
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| language | English |
| last_indexed | 2024-03-11T06:03:48Z |
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| spelling | doaj.art-ffdc044b88ff4273ab1c63655ced37ba2023-11-17T13:12:35ZengMDPI AGPharmaceuticals1424-82472023-03-0116342310.3390/ph16030423SPECT Imaging with Tc-99m-Labeled HYNIC-FAPI-04 to Extend the Differential Time Window in Evaluating Tumor FibrosisXiu Luo0Zhe Zhang1Chao Cheng2Tao Wang3Danzhou Fang4Changjing Zuo5Gengbiao Yuan6Rou Li7Xiao Li8Department of Nuclear Medicine, Shanghai Changhai Hospital, Shanghai 200433, ChinaDepartment of Nuclear Medicine, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, ChinaDepartment of Nuclear Medicine, Shanghai Changhai Hospital, Shanghai 200433, ChinaDepartment of Nuclear Medicine, Shanghai Changhai Hospital, Shanghai 200433, ChinaDepartment of Nuclear Medicine, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, ChinaDepartment of Nuclear Medicine, Shanghai Changhai Hospital, Shanghai 200433, ChinaDepartment of Nuclear Medicine, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, ChinaDepartment of Nuclear Medicine, Shanghai Changhai Hospital, Shanghai 200433, ChinaDepartment of Nuclear Medicine, Shanghai Changhai Hospital, Shanghai 200433, ChinaThe so-far used Ga-68- or F-18-labelled tracers are of a relative short time window in differentiating tumor fibrosis. SPECT applicable imaging probe, <sup>99m</sup>Tc-HYNIC-FAPI-04, was synthesized and evaluated in tumor cells and animal models of FAP-positive glioma and FAP-negative hepatoma, and then compared with <sup>18</sup>F-FDG or <sup>68</sup>Ga-FAPI-04 PET/CT. The radio-labeling rate of <sup>99m</sup>Tc-HYNIC-FAPI-04 was greater than 90%, and the radiochemical purity was >99% after purification with sep-pak C18 column. In vitro cell uptake experiments of <sup>99m</sup>Tc-HYNIC-FAPI-04 showed good FAP binding specificity, and the cellular uptake significantly decreased when blocked by DOTA-FAPI-04, reflecting the similar targeting mechanism of HYNIC-FAPI-04 and DOTA-FAPI-04. SPECT/CT imaging showed that U87MG tumor was distinguishable and of a high uptake of <sup>99m</sup>Tc-HYNIC-FAPI-04 (2.67 ± 0.35 %ID/mL at 1.5 h post injection (h P.I.), while tumor signal of FAP-negative HUH-7 was as low as 0.34 ± 0.06 %ID/mL. At 5 h P.I., U87MG tumor was still distinguishable (1.81 ± 0.20 %ID/mL). In comparison, although U87MG tumor was of obvious <sup>68</sup>Ga-FAPI-04 uptake and clearly visible at 1 h P.I., the tumorous radioactive signals were fuzzy at 1.5 h P.I. <sup>99m</sup>Tc-HYNIC-FAPI-04 specifically bound to FAP-positive tumors and qualified with the ability of evaluating tumor fibrosis over longer time windows.https://www.mdpi.com/1424-8247/16/3/423<sup>99m</sup>Tc-HYNIC-FAPI-04differential time windowtumor fibrosisfibroblast activating proteinFAP inhibitorFAPI-04 |
| spellingShingle | Xiu Luo Zhe Zhang Chao Cheng Tao Wang Danzhou Fang Changjing Zuo Gengbiao Yuan Rou Li Xiao Li SPECT Imaging with Tc-99m-Labeled HYNIC-FAPI-04 to Extend the Differential Time Window in Evaluating Tumor Fibrosis Pharmaceuticals <sup>99m</sup>Tc-HYNIC-FAPI-04 differential time window tumor fibrosis fibroblast activating protein FAP inhibitor FAPI-04 |
| title | SPECT Imaging with Tc-99m-Labeled HYNIC-FAPI-04 to Extend the Differential Time Window in Evaluating Tumor Fibrosis |
| title_full | SPECT Imaging with Tc-99m-Labeled HYNIC-FAPI-04 to Extend the Differential Time Window in Evaluating Tumor Fibrosis |
| title_fullStr | SPECT Imaging with Tc-99m-Labeled HYNIC-FAPI-04 to Extend the Differential Time Window in Evaluating Tumor Fibrosis |
| title_full_unstemmed | SPECT Imaging with Tc-99m-Labeled HYNIC-FAPI-04 to Extend the Differential Time Window in Evaluating Tumor Fibrosis |
| title_short | SPECT Imaging with Tc-99m-Labeled HYNIC-FAPI-04 to Extend the Differential Time Window in Evaluating Tumor Fibrosis |
| title_sort | spect imaging with tc 99m labeled hynic fapi 04 to extend the differential time window in evaluating tumor fibrosis |
| topic | <sup>99m</sup>Tc-HYNIC-FAPI-04 differential time window tumor fibrosis fibroblast activating protein FAP inhibitor FAPI-04 |
| url | https://www.mdpi.com/1424-8247/16/3/423 |
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